The main biosynthetic task of the bacterium Escherichia coli is protein
production. This requires energy generation (grey arrow), carbon-skeleton synthesis,
nitrogen incorporation to make amino acids, and protein synthesis. The anabolic fluxes
(red, green and blue arrows) increase linearly with growth rate, as does the required
anabolic proteome fraction except for processes that are directly slowed by nutrient
limitation (such as amino-acid synthesis during nitrogen limitation). Carbon catabolism
provides energy and building blocks for anabolism, and cAMP allocates the proper fraction
of the proteome to carbon-catabolic enzymes. You et al.3 find that this is achieved by a new regulatory
loop, wherein α-ketoacids inhibit cAMP production: when favoured carbon sources
such as glucose are present or nitrogen is limiting, carbon influx exceeds anabolic
capability and α-ketoacid accumulation inhibits cAMP. Conversely, when favoured
carbon sources are depleted, α-ketoacid levels fall, and cAMP increases to
stimulate production of the required carbon-catabolic machinery (orange arrows).